Cells Commons^™

Effectiveness Of Stabilized Hypochlorous Acid In Acute Peritonitis Treatment: A Murine Surgical Study, Benjamin Michael Pomeroy

Graduate Theses/Dissertations

Peritonitis is an inflammatory condition affecting the mesothelial cells that line the peritoneal cavity and is commonly induced by bowel perforations. This medical emergency is treated through antibiotic therapy and surgical intervention followed by tissue irrigation (lavage). Acute treatments aim to remove the bacterial burden, however recurring peritoneal infections occur at high rates and contribute to patient morbidity. These recurring infections are likely due to the inability of lavage solutions to remove the entire massive intra-abdominal bacterial load due to intestinal perforation. Numerous antiseptic solutions and antibiotic additives have been evaluated in their ability to improve source control by abdominal …

Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker

Theses & Dissertations

Melanoma is the deadliest form of skin cancer, and incidence has continued to increase. Half of all melanomas have a BRAF V600E mutation and respond to MAPK pathway inhibitors, including BRAF inhibitor therapy or BRAF/MEK inhibitor combination therapy, but nearly all patients develop treatment resistance. Melanoma cell lines produce variable results as models of MAPK pathway inhibitor resistance. To better understand how the genomic similarity of a melanoma cell line to patient-derived tumors affects resistance mechanisms, differences in DNA mutations and copy-number alterations were compared between melanoma cell lines profiled by the Cancer Cell Line Encyclopedia and cutaneous melanoma tumors …

Mutational And Biophysical Robustness In A Prestabilized Monobody, Peter G. Chandler, Li Lynn Tan, Benjamin T. Porebski, James S. Green, Blake T. Riley, Sebastian S. Broendum, David E. Hoke, Robert J. Falconer, Trent P. Munro, Malcolm Buckle, Colin J. Jackson, Ashley M. Buckle

Advanced Science Research Center

The fibronectin type III (FN3) monobody domain is a promising non-antibody scaffold, which features a less complex architecture than an antibody while maintaining analogous binding loops. We previously developed FN3Con, a hyperstable monobody derivative with diagnostic and therapeutic potential. Prestabilization of the scaffold mitigates the stability–function trade-off commonly associated with evolving a protein domain toward biological activity. Here, we aimed to examine if the FN3Con monobody could take on antibody-like binding to therapeutic targets, while retaining its extreme stability. We targeted the first of the Adnectin derivative of monobodies to reach clinical trials, which was engineered by directed evolution for …

Effects Of Alternative Chemotherapeutic Agents On Thyroid Cancer Cell Line Ml-1, Husref Rizvanovic

Graduate Theses/Dissertations

Though differentiated thyroid carcinomas have decent prognosis when detected early, radioactive iodine (RAI) resistant and advanced thyroid cancers are still difficult to treat with existing therapies. Better therapeutic agents are needed. Studies have shown that aggressive thyroid cancers (ML-1) express the extracellular matrix protein, matrix metalloproteinase (MMP-2). MMP-2 has been linked to metastasis and aggressiveness of several cancers and has been shown to play a crucial role in tumor invasion. Chlorotoxin is a selective MMP-2 receptor agonist, and Saporin is a well-known ribosome-inactivating protein used for anti-cancer treatment; however, these two agents have never been studied when conjugated together. I …

Tunable Multiphase Dynamics Of Arginine And Lysine Liquid Condensates, Rachel S. Fisher, Shana Elbaum-Garfinkle

Advanced Science Research Center

Liquid phase separation into two or more coexisting phases has emerged as a new paradigm for understanding subcellular organization, prebiotic life, and the origins of disease. The design principles underlying biomolecular phase separation have the potential to drive the development of novel liquid-based organelles and therapeutics, however, an understanding of how individual molecules contribute to emergent material properties, and approaches to directly manipulate phase dynamics are lacking. Here, using microrheology, we demonstrate that droplets of poly-arginine coassembled with mono/polynucleotides have approximately 100 fold greater viscosity than comparable lysine droplets, both of which can be finer tuned by polymer length. We …

Single-Molecule Analysis Of Subtelomeres And Telomeres In Alternative Lengthening Of Telomeres (Alt) Cells, Heba Z. Abid, Jennifer Mccaffrey, Kaitlin Raseley, Eleanor Young, Katy Lassahn, Dharma Varapula, Harold Riethman, Ming Xiao

School of Medical Diagnostics & Translational Sciences Publications

BACKGROUND: Telomeric DNA is typically comprised of G-rich tandem repeat motifs and maintained by telomerase (Greider CW, Blackburn EH; Cell 51:887-898; 1987). In eukaryotes lacking telomerase, a variety of DNA repair and DNA recombination based pathways for telomere maintenance have evolved in organisms normally dependent upon telomerase for telomere elongation (Webb CJ, Wu Y, Zakian VA; Cold Spring Harb Perspect Biol 5:a012666; 2013); collectively called Alternative Lengthening of Telomeres (ALT) pathways. By measuring (TTAGGG) n tract lengths from the same large DNA molecules that were optically mapped, we simultaneously analyzed telomere length dynamics and subtelomere-linked structural changes at a large …

The Revolution Will Be Open-Source: How 3d Bioprinting Can Change 3d Cell Culture, Robert D. Bruno, John Reid, Patrick C. Sachs

School of Medical Diagnostics & Translational Sciences Publications

(First paragraph) The development of three-dimensional culture scaffolds represents a revolutionary step forward for in vitro culture systems. Various synthetic and naturally occurring substrates have been developed that support 3D growth of cells. In most fields, including mammary gland biology and tumorigenesis, the two most common substrates used are the basement membrane rich extracellur matrix (ECM) isolated from EngelbrethHolm-Swarm (EHS) mouse sarcomas (e.g. Matrigel) and collagen extracted from rat-tails. The processes of 3D culture in these two substrates has remained unchanged for nearly half a century: cells are either mixed with unpolymerized matrix to disperse them randomly throughout the substrate …

Illumination Of The Golgi Apparatus Of Pathogenic And Nonpathogenic Naegleria Species, Tyler M. Poe

Theses and Dissertations

In this study, Naegleria fowleri, a pathogenic amoeba and the causative agent of Primary Amebic Meningoencephalitis (PAM), was utilized to determine the presence or absence of classically conserved Golgi molecules featured in the expression of a Golgi apparatus. Previous studies concluded no Golgi expression via light microscopy and transmission electron microscopy, but a recent report on Naegleria gruberi indicated the presence of dispersed Golgi tubules. Non-pathogenic species of the Naegleria genus such as Naegleria gruberi 30540 and Naegleria lovaniensis 30569 were utilized in Western immunoblot analysis compared to reduced whole-cell lysate proteins of two strains of N. fowleri and …

The Systemic Quantification Of Immune Cell Populations In Various Murine Models: How Age, Tumor Burden, And Immunotherapy Affect The Immune Response, Kavita Sinha

Honors Scholar Theses

Immunotherapy as a form of cancer treatment has become increasingly popular in the past few decades. Researchers have worked to figure out how to best use the body’s natural defense mechanism, the immune system, to fight off and destroy cancer cells. In particular, the goal has been to manipulate checkpoint blockades such as CTLA-4 and PD-1 in order to take the breaks off of the immune system, allowing for a prolonged immune response to the cancer. This work has led to the development of human versions of anti-CTLA4 antibodies (ipilimumab, tremelimumab) and anti-PD1 antibodies (pembrolizumab and Nivolumab) that are currently …

Family Strategies To Support Siblings Of Pediatric Hematopoietic Stem Cell Transplant Patients., Taylor E. White, Kristopher A. Hendershot, Margie D. Dixon, Wendy Pelletier, Ann Haight, Kristin Stegenga, Melissa A. Alderfer, Lydia Cox, Jeffrey M. Switchenko, Pamela Hinds, Rebecca D. Pentz

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To describe the strategies families report using to address the needs and concerns of siblings of children, adolescents, and young adults undergoing hematopoietic stem cell transplant (HSCT).

METHODS: A secondary semantic analysis was conducted of 86 qualitative interviews with family members of children, adolescents, and young adults undergoing HSCT at 4 HSCT centers and supplemented with a primary analysis of 38 additional targeted qualitative interviews (23 family members, 15 health care professionals) conducted at the primary center. Analyses focused on sibling issues and the strategies families use to address these issues.

RESULTS: The sibling issues identified included: (1) feeling …

Taurine's Effect On Cocaine Reward And Neurogenesis In The Adolescent Male Rat Brain., Avery E. Villa-Gonzalez

Dissertations and Theses

Adolescence is a developmentally critical transition from childhood to adulthood including both maturation of the body and the brain. Neuroplastic changes result in dynamic organization of the brain during adolescence, leaving them vulnerable to development of mental illness and drug-seeking behavior. According to the United Nations Office on Drugs and Crime, the psychostimulant cocaine is the second most popular illicit drug in the world. Cocaine, amongst having many detrimental effects, has shown to also decrease hippocampal neurogenesis, resulting in decreased neuroplasticity and cognitive dysfunction. Previous students in our laboratory have shown that treatment of adult male rats with the essential …

Inhibition Of Human Α7 Nicotinic Acetylcholine Receptors By Cyclic Monoterpene Carveol, Yusra Lozon, Ahmed Sultan, Stuart J. Lansdell, Tatiana Prytkova, Bassem Sadek, Keun-Hang Susan Yang, Frank Christopher Howarth, Neil S. Millar, Murat Oz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Cyclic monoterpenes are a group of phytochemicals with antinociceptive, local anesthetic, and anti-inflammatory actions. Effects of cyclic monoterpenes including vanilin, pulegone, eugenole, carvone, carvacrol, carveol, thymol, thymoquinone, menthone, and limonene were investigated on the functional properties of the cloned α₇ subunit of the human nicotinic acetylcholine receptor expressed in Xenopus oocytes. Monoterpenes inhibited the α₇ nicotinic acetylcholine receptor in the order carveol>thymoquinone>carvacrol>menthone>thymol>limonene>eugenole>pulegone≥carvone≥vanilin. Among the monoterpenes, carveol showed the highest potency on acetylcholine-induced responses, with IC₅₀ of 8.3 µM. Carveol-induced inhibition was independent of the membrane potential and could not be …

Abcb5 Identifies Immunoregulatory Dermal Cells, Tobias Schatton, Jun Yang, Sonja Kleffel, Mayuko Uehara, Steven R. Barthel, Christoph Schlapbach, Qian Zhan, Stephen Dudeney, Hansgeorg Mueller, Nayoung Lee, Juliane C. De Vries, Barbara Meier, Seppe Vander Beken, Mark M. Kluth, Christoph Ganss, Arlene H. Sharpe, Ana Maria Waaga-Gasser, Mohamed H. Sayegh, Reza Abdi, Karin Scharffetter-Kochanek, George F. Murphy, Thomas S. Kupper, Natasha Y. Frank, Markus H. Frank

Research outputs 2014 to 2021

Cell-based strategies represent a new frontier in the treatment of immune-mediated disorders. However, the paucity of markers for isolation of molecularly defined immunomodulatory cell populations poses a barrier to this field. Here, we show that ATP-binding cassette member B5 (ABCB5) identifies dermal immunoregulatory cells (DIRCs) capable of exerting therapeutic immunoregulatory functions through engagement of programmed cell death 1 (PD-1). Purified Abcb5+ DIRCs suppressed T cell proliferation, evaded immune rejection, homed to recipient immune tissues, and induced Tregs in vivo. In fully major-histocompatibility-complex-mismatched cardiac allotransplantation models, allogeneic DIRCs significantly prolonged allograft survival. Blockade of DIRC-expressed PD-1 reversed the inhibitory effects of …

Stem Cells As A Cure For Amyotrophic Lateral Sclerosis, Chaya K. Hirsch

The Science Journal of the Lander College of Arts and Sciences

Amyotrophic Lateral Sclerosis (ALS) is a fatal motor neuron disease which affects approximately 30,000 Americans at any given time (alsa.org, 2010). The etiology of this terminal disease unfortunately remains an unsolved mystery and has therefore severely limited the ability to find a cure. The use of stem cells to regenerate neurons has been vastly studied and have produced very promising results. However, its practicality as a cure or treatment for neurodegenerative diseases, such as ALS, is greatly compromised. Three different therapies involving stem cells were examined, Embryonic Stem Cells (ESC), induced pluripotent stem cells, (iPSC) and direct reprogramming of adult …

Chemopreventive Effects Of Pterostilbene In Metastatic Prostate Cancer Cells, Phillip A. Zook

PCOM Biomedical Studies Student Scholarship

Recent studies find that pterostilbene (PTS) exhibits more favorable drug properties and similar chemopreventive effects to its structural analogue resveratrol (RSV). However, few studies describe the activity of PTS in prostate cancer (PCa). Here, we conducted cell count experiments to assess the effects of PTS on metastatic PCa cell viability and to compare the potency of PTS to RSV in this respect. We also performed experiments to assess the effects of PTS on the androgen receptor (AR) and AR-mediated events. We used qPCR to measure the mRNA levels of the androgenresponsive gene (ARG), prostate-specific antigen (PSA), and Western blots to …

Cardiac Tissue Regeneration - The Use Of Stem Cells, Chavy Friedlander

The Science Journal of the Lander College of Arts and Sciences

The following is the introduction to the article: Cardiovascular disease is the leading cause of illness and fatality. Diseases such as coronary artery disease, myocardial infarction and subsequent congestive heart failure pose a serious problem to much of the population in the Unites States and all over the world. The heart’s compromised function that results from the above conditions is so influential as the heart has little capacity to repair its lost tissue; once the cardiac myocytes are destroyed its effects are amplified by a drastic decrease in cardiac function. Until recently with the advent of stem cell technology, researchers …